Benzodiazepine (BZP) derivatives represented by diazepam have been used as, for example, anxiolytic agents. BZP agents exhibit excellent anxiolytic activity in human beings, whereas they are known to cause undesirable adverse reactions (side effects) such as sedation, muscle-relaxation and interaction with alcohol/barbiturates. Therefore, the development of anxioselective anxiolytic agents with less side effects than conventional BZP derivatives has been desired.
On the other hand, it has been proved that receptors which have specific affinity for BZP derivatives exist in the central nervous system by a late pharmacological study [Science, vol. 198, 848 (1977)]. The findings of BZP receptors in the central nervous system have remarkably advanced the research on the mechanism of BZP agents. It was suggested that the BZP receptor forms a complex with the .gamma.-aminobutyric acid (GABA) receptor and the Cl.sup.- ionophore, and BZPs exhibit pharmacological activity through the GABA response. That is, the compounds which act on the BZP receptors can be classified with different efficacy on a continuum from full agonists to inverse agonists, according to their modulatory effects on GABAergic transmission. Furthermore, they are classified into full agonists, partial agonists, antagonists, partial inverse agonists and inverse agonists in consideration of their behavioral pharmacological properties.
Recently, research works have emphasized the search for anxiolytic agents which selectively act on anxiety and have less side effects such as sedation, muscle-relaxation, potentiation of alcoholic effect or dependency liability associated with BZP agents. In the process of these investigations, many compounds have been found which possess high affinity for BZP receptors in spite of their different structures from BZP (U.S. Pat. No. 4,849,421, U.S. Pat. No. 4,965,264 and U.S. Pat. No. 5,153,194). Among them, the compounds classified into BZP partial agonists have become important as a new type of anxiolytic agents since they are dissociated from side effects but exhibit selective pharmacological activity against anxiety.